The four partners in this ISAAC Unit application, Kilimanjaro Christian Medical Centre (KCMC), Kibongoto National Tuberculosis Hospital (KNTH), KIWAKKUKI and Duke University Medical Center wish to expand their studies of AIDS-associated co-infections. Tanzania is an area with extraordinary need for HIV/AIDS-related care, and is listed among the 14 countries in the President's Emergency Plan for AIDS Relief. These partners have existing research collaborations investigating AIDS-associated co-infections that have generated the preliminary data in this application. A broad spectrum of co-infections will be studied, including MTB, malaria, bacterial and non-malarial protozoa, fungi, and human papillomavirus involving the female genital tract, reflecting the diverse research expertise of the ISAAC Unit partners. Expertise in HIV viral and immune pathogenesis will offer outstanding insights into HIV/Co-Pathogen interactions. A Pediatric Scientific Program will ensure the opportunity to study age-specific co-infections, and community participation will be solicited through the Community Relations/Education Administrative Program. During year 1 of the ISAAC Unit, our goal will focus on expanding research infrastructure through training and the purchase of key laboratory equipment. Research training will be provided through didactic presentations and site monitoring by Pharmaceutical Product Development, and twinning between U.S. and Tanzanian personnel will provide ongoing support. During years 2-4 the ISAAC Unit Scientific Programs will generate concept proposals for specific research projects, and 24 concept proposals are included with this application as examples of the research creativity and capabilities of ISAAC Unit investigators. These concept proposals will be reviewed by the Principal Investigators, and with the guidance of the ISAAC Unit Scientific Advisory Committee, select proposals will be funded. Logistic assistance to ensure the efficient conduct of ISAAC Unit research will be provided by the Administrative Programs, and the Principal Investigators will hold research projects to a timeline, leading to the publication of research results. In summary, substantial research infrastructure, experience and collaboration among the four partners is currently available. Award of an ISAAC Unit will allow these partners to dramatically expand research by providing a scientific and administrative support organization, well-trained personnel for the conduct of research, laboratory equipment and research funding. [unreadable] [unreadable]